Objectives: 1. To determine the factors which contribute to virulence and tissue invasiveness of Entamoeba histolytica. Methods: 1. Culture axenically pathogenic strains of E. histolytica; 2. Examine by light and electron microscopy, tissue and cellular responses to intact and viable amebae, the mechanically disrupt organisms, to amebae-free culture supernatant, to isolated amebic cell membranes, and to soluble components of mechanically disrupted trophozoites in the following models: a. hamster liver (in vitro injection); b. hamster large intestine (intrececal injection); c. hamster and human colonic mucosal organ cultures (in vitro); 3. Separate, purify, and concentrate soluble toxin(s) with a combination of biochemical methods including density gradient centrifugation, gel filtration, and disc gel electrophoresis; 4. Characterize purified toxin(s) by migration in disc gel electrophoresis, comparison with marker proteins of known molecular weight, heat sensitivity, inactivation by human amebic antiserum, dializability, and effect on fluid secretion in ligated rabbit colonic loop preparation; 5. Apply human serum to organ culture infected with E. histolytica to determine if enhanced virulence is observed.